The purpose of the proposed project is to seek and identify genetic factors which may be operative in conditioning the mammalian host's resistance to the lethal effects of severe thermal injury. Preliminary studies in this laboratory have uncovered evidence of the existence of certain highly inbred strains of rats which exhibit a high level of resistance to the lethality of severe thermal injury. In contrast, another highly inbred rat strain has been shown to be exquisitely susceptible to the same level of thermal injury, administered under comparable experimental conditions. Two outbred strains of rats studied concurrently have exhibited intermediate degrees of resistance to severe injury. Recent progress in the understanding of the immunogenetics of the major histocompatibility complex in rats, taken together with the association of host immune responsiveness determinants with certain components of the MHC suggest that some of the differences in MHC genotypes encountered in the rat strains used in the present study may be related to the outcome of these experiments. This possibility, and the potential role of certain alleles of the main histocompatibility complex as possible determinants of host resistance to tissue injury will undergo systematic study during the proposed project period.